Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6 (ALKBH6)

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6 (ALKBH6) is a human enzyme belonging to the AlkB family of Fe(II)/alpha-ketoglutarate-dependent dioxygenases. It features a characteristic double-stranded beta-helix (DSBH) fold and several unique structural elements (notably the Flip1, Flip2, and Flip3 domains) that influence substrate specificity. ALKBH6 is implicated in the direct repair of alkylated nucleic acids, likely through demethylation reactions that reverse nucleic acid methylation damage. While its exact physiological substrates remain unidentified, ALKBH6 shows a preference for single-stranded nucleic acids. Functionally, it participates in maintenance of genomic stability and has a role in tumor suppression, as loss or mutation of ALKBH6 leads to increased DNA damage sensitivity and is linked to poor cancer outcomes. The protein interacts with histone modification reader ZMYND11, suggesting a cross-talk between RNA/DNA modification and epigenetic regulation. No direct drugs or inhibitors are currently documented for ALKBH6, but its role in cancer biology and DNA repair marks it as a molecule of potential therapeutic interest.

Other names

AlkB homolog 6Probable RNA/DNA demethylase ALKBH6ABH6MGC15677Alkylated DNA repair protein alkB homolog 6Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6Probable nucleic acid dioxygenase ALKBH6Putative RNA/DNA demethylase ALKBH6Alkylation repair homolog 6

Not established for drugs, but the enzyme putatively acts by catalyzing demethylation of nucleic acids using Fe(II) and alpha-ketoglutarate as cofactors